Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Nemiralisib, Dose-Finding, GSK2269557, Acute Moderate or Severe Exacerbation of Chronic Obstructive Pulmonary Disease
Brief summary
Nemiralisib is being developed as an anti-inflammatory drug for the treatment of inflammatory airways disease. This study is designed to assess the dose response, efficacy, safety, and pharmacokinetics of nemiralisib across a range of doses \[up to 750 micrograms (µg)\] compared with placebo. The study consists of a Screening Period, a 12-Week Treatment Period and a 12-Week Post-Treatment Follow-Up Period. Approximately 1,250 subjects with an acute moderate or severe exacerbation of COPD requiring standard of care (SoC) therapy will be randomized in this double-blind study. Subjects will be randomized to receive different doses of nemiralisib or placebo via ELLIPTA® inhaler. The total duration of study participation is approximately 6 months (170 days). ELLIPTA is the registered trademark of GlaxoSmithKline (GSK) group of companies.
Interventions
DRUGPlacebo ELLIPTA
Placebo will be administered via oral inhalation route once daily in the morning.
DRUGNemiralisib ELLIPTA 50 µg
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 50 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
DRUGNemiralisib ELLIPTA 100 µg
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 100 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
DRUGNemiralisib ELLIPTA 250 µg
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 250 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
DRUGNemiralisib ELLIPTA 500 µg
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 500 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
DRUGNemiralisib ELLIPTA 750 µg
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 750 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
DRUGAlbuterol (Salbutamol) MDI or nebules
Albuterol (Salbutamol) MDI or nebules will be provided to all subjects as a rescue medication.
SoC therapy for the index exacerbation is defined as treatment with oral/systemic corticosteroid (prednisone 40 mg/day or equivalent) for 5 days and antibiotic for 7 days. Subjects will receive SoC as prescribed by the Investigator or medically qualified designee. The dose and/or duration of prednisone and/or the antibiotic can be modified according to the Investigator's/medically qualified designee's judgment or according to local country/institution practice.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double blind, sponsor- open study.
Intervention model description
Subjects will be randomized to receive either nemiralisib (50-750 µg) or placebo in a parallel group.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 40 to 80 years of age, inclusive, at Screening (Visit 1). * An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society \[ global initiative for chronic obstructive lung disease (GOLD), 2017\] as follows: Chronic obstructive pulmonary disease is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. * Current or former cigarette smoker with a history of cigarette smoking of \>=10 pack-years. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (Visit 1). Number of pack years = (number of cigarettes per day / 20) x number of years smoked). * Acute exacerbation of COPD requiring an escalation in therapy to include oral/systemic corticosteroid(s) (prednisone 40 mg/day or equivalent) for 5 days and antibiotic(s) for 7 days; the dose and/or duration of prednisone (40 mg/day or equivalent) and/or the antibiotic can be modified according to the Investigator's/medically qualified designee's judgment or according to local country/institution practice. Acute exacerbation to be confirmed by an experienced physician and to represent a recent worsening of at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. Major symptoms include subjective increase in dyspnea, increase in sputum volume or change in sputum color. Minor symptoms include increased cough, increased wheeze, sore throat, colds or fever (oral temperature \>37.5 degree Celsius) without other cause. * Body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 16 - 35 kg per meter square (kg/m\^2) (inclusive) * Male and female subjects are eligible to participate in the study. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the 12-Week Double-Blind Treatment Period and for at least 5 half-lives (10 days) after the last of double-blind study treatment. * Capable of giving signed informed consent.
Exclusion criteria
* Current diagnosis of asthma, according to the Global Initiative for Asthma (GINA, 2017). Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD. * Potential of hydrogen (pH) \< 7.30 or the need for invasive mechanical ventilation. * Moderate/severe exacerbation of COPD for which SoC was started \>48 hours since diagnosis. * A chest X-ray \[or computed tomography (CT) scan\] that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray (or CT scan) must be taken at Screening (Visit 1). For sites in Germany: if a chest X-ray (or CT scan) within 1 year of Screening (Visit 1) is not available, approval to conduct a diagnostic chest X-ray (CT scan) will need to be obtained from the Federal Office for Radiation Protection (BfS). * Clinically significant pneumonia, identified by chest X-ray (CT scan) at Screening. * A diagnosis of alpha 1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, clinically overt bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), primary pulmonary hypertension, interstitial lung diseases,or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results. * A history or current evidence of clinically significant and unstable disease such as cardiovascular (e.g., subjects requiring implanted cardioverter defibrillator \[ICD\], pacemaker requiring a rate set \>60 beats per minute (bpm), uncontrolled hypertension, New Your Heart Association Class IV \[NYHA, 1994\], known left ventricular ejection fraction \<30 percent) neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or hematological abnormalities. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. (Note: subjects with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or noninsulin-dependent diabetes mellitus \[NIDDM\]) are permitted to be entered into the study). * Having undergone lung volume reduction surgery or lung resection for any other reason e.g. lung carcinoma * Liver diseases including ALT\>2x upper limit of normal (ULN); Total bilirubin \>1.5xULN (Isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent); current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study treatment; Positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment. * Positive hepatitis C ribonucleic acid (RNA) test result at Screening or within 3 months prior to first dose of study treatment. * Carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin are not excluded if the subject has been considered cured within 5 years since diagnosis. * History of allergy or hypersensitivity to any of the study medications \[e.g. beta-agonists, Phosphoinositide 3-Kinase Delta (PI3Kd) inhibitors\] or components of the inhalation powder (e.g., lactose). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the investigator, contraindicates the subject's participation are excluded. * Strong inhibitors of cytochrome P450 3A4 (CYP3A4) including antiretrovirals including protease inhibitors; Oral antifungal treatments such as ketoconazole and itraconazole. It is recommended that posaconazole is used as the oral antifungal treatment of choice. Short courses of up to 14 days are allowed for fluconazole and voriconazole, but chronic administrations are not permitted; Antibiotics such as telithromycin and troleandomycin (macrolide). It is recommended that azithromycin is used as the macrolide antibiotic of choice. Short courses up to 14 days are allowed for mibefradil (calcium channel blocker), erythromycin and clarithromycin (including intravenous clarithromycin) but chronic administrations are not permitted; Anti-epileptic treatments; and anti-tuberculosis therapy. These medications must all have been stopped at least 14 days prior to first dose of study treatment. Use of sensitive narrow therapeutic index CYP3A4 substrates including alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus; Intravenous theophylline will be allowed but only under strict therapeutic drug monitoring for signs of theophylline toxicity as a result of co-administration with nemiralisib; Subjects may be recruited into the study already under treatment with theophylline or started on theophylline following the start of treatment and before the end of 14 days post last dose. * Chronic treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for \>15 hours a day. Oxygen prn use (\<=15 hours per day) is not exclusionary. Oxygen use during an exacerbation is permitted. * Chronic treatment with anti-Tumor Necrosis Factor (anti-TNF), anti-Interleukin-1 (anti-IL1), or any other immunosuppressive therapy within 60 days prior to the first dose of double-blind study treatment. * Clinically significant sleep apnea that requires the use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) for \> 48 hours. * Any other investigational treatment within the following time periods prior to the first dose of double-blind study treatment in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product, whichever is longer. Note: subjects who participated in a previously completed study and/or were withdrawn from an ongoing study that included/includes nemiralisib are excluded from participating in this study. * Exposure to more than 4 investigational medicinal products within 12 months prior to the first dose of double-blind study treatment in the current study. * A clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | Baseline and Day 84 | FEV1 is maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via one nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CAT Total Score | Baseline and at Days 28, 56 and 84 | The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score was calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is defined as CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented. |
| Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Up to Week 16 | The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening, Days 14, 84, 112 and at early withdrawal | A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented. |
| Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Upto Week 16 | Blood samples were collected for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. |
| Number of Participants With Worst Case Post Baseline Hematology Values | Upto Week 16 | Blood samples were collected for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. |
| Number of Participants Reporting COPD Exacerbations | Up to Week 16 | Participants reporting acute COPD exacerbations during the study period has been presented. |
| Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | Up to Week 12 | Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented. |
| Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | Up to Week 12 | Number of participants with time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. |
| Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Baseline and Days 14, 28, 56 (pre and post bronchodilaor), 84 (pre-bronchodilator) and at hospital discharge (maximum 24 Weeks) | Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1. |
| Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Baseline and pre- and post-bronchodilator on Days 14, 28, 56 and 84 | Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10 to 30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1. |
| Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Days 14, 28, 56 and 84 | EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score \>=9 points from maximum observed value, sustained for \>=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. |
| Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | From randomization to Week 12 | Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score \>=9 points from the Maximum Observed Value, sustained for \>=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented. |
| Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Up to Week 12 | Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation. |
| Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Days 28, 56 and 84 | The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score \>=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score \>=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. |
| Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Days 28, 56 and 84 | SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score \>=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score \>=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. |
| Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Baseline and Days 28, 56 and 84 | SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100 multiplied by summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is defined as SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented |
| Mean Number of Occasions of Rescue Medication Use Per Day | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period | Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose. |
| Percentage of Rescue-free Days | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period | Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose. |
| Plasma Concentration of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received. |
| Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Up to Week 24 | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed. |
| Time to Reach Cmax (Tmax) of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed. |
| Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed. |
| Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed. |
| AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28 | Plasma samples were collected at indicated time points and analyzed. |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Mexico, Netherlands, Poland, Romania, Russia, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase IIb, multicenter, randomized, stratified, double-blind (sponsor open), placebo controlled parallel-group study in participants who presented with an acute moderate or severe exacerbation of chronic obstructive pulmonary disease (COPD) requiring Standard of Care (SoC).
Pre-assignment details
A total of 943 participants were randomized, and 938 participants who received at least one dose of study treatment were included in the modified intent to treat (MITT) Population. The study included participants enrolled from 16 countries.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication. | 276 |
| Nemiralisib 12.5 mcg Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 22 |
| Nemiralisib 50 mcg Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 91 |
| Nemiralisib 100 mcg Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 92 |
| Nemiralisib 250 mcg Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 90 |
| Nemiralisib 500 mcg Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 89 |
| Nemiralisib 750 mcg Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication. | 278 |
| Total | 938 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 | 5 | 4 | 6 | 5 | 16 |
| Overall Study | Lack of Efficacy | 1 | 1 | 1 | 1 | 1 | 0 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 0 | 1 | 2 | 3 |
| Overall Study | Physician Decision | 3 | 1 | 0 | 0 | 1 | 2 | 3 |
| Overall Study | Protocol-defined stopping criteria | 9 | 0 | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 | 1 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 1 | 5 | 6 | 3 | 6 | 16 |
Baseline characteristics
| Characteristic | Placebo | Total | Nemiralisib 750 mcg | Nemiralisib 500 mcg | Nemiralisib 250 mcg | Nemiralisib 100 mcg | Nemiralisib 50 mcg | Nemiralisib 12.5 mcg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.4 Years STANDARD_DEVIATION 7.94 | 65.0 Years STANDARD_DEVIATION 7.68 | 64.8 Years STANDARD_DEVIATION 7.61 | 64.9 Years STANDARD_DEVIATION 8.04 | 66.0 Years STANDARD_DEVIATION 6.94 | 65.1 Years STANDARD_DEVIATION 7.43 | 63.1 Years STANDARD_DEVIATION 7.61 | 67.8 Years STANDARD_DEVIATION 7.2 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 15 Participants | 6 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 18 Participants | 66 Participants | 19 Participants | 7 Participants | 9 Participants | 2 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian-South East Asian Heritage | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 14 Participants | 6 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White-Arabic/North African Heritage | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White-White Caucasian/European Heritage | 252 Participants | 835 Participants | 246 Participants | 76 Participants | 79 Participants | 86 Participants | 79 Participants | 17 Participants |
| Sex: Female, Male Female | 86 Participants | 309 Participants | 100 Participants | 22 Participants | 31 Participants | 29 Participants | 35 Participants | 6 Participants |
| Sex: Female, Male Male | 190 Participants | 629 Participants | 178 Participants | 67 Participants | 59 Participants | 63 Participants | 56 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 276 | 0 / 22 | 3 / 91 | 1 / 92 | 0 / 90 | 0 / 89 | 1 / 278 |
| other Total, other adverse events | 31 / 276 | 1 / 22 | 14 / 91 | 19 / 92 | 25 / 90 | 36 / 89 | 101 / 278 |
| serious Total, serious adverse events | 23 / 276 | 2 / 22 | 9 / 91 | 13 / 92 | 16 / 90 | 6 / 89 | 26 / 278 |
Outcome results
Primary
Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator
FEV1 is maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via one nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented.
Time frame: Baseline and Day 84
Population: MITT Population consisted of all randomized participants who received at least 1 dose of study treatment.. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.052 Liters |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.031 Liters |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.026 Liters |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.014 Liters |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.058 Liters |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.049 Liters |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.049 Liters |
95% CI: [-0.143, 0.103]
95% CI: [-0.098, 0.036]
95% CI: [-0.102, 0.028]
95% CI: [-0.064, 0.071]
95% CI: [-0.075, 0.061]
95% CI: [-0.051, 0.042]
Secondary
Change From Baseline in CAT Total Score
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score was calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is defined as CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented.
Time frame: Baseline and at Days 28, 56 and 84
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -4.6 Scores on a scale |
| Placebo | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -4.2 Scores on a scale |
| Placebo | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -4.7 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -1.9 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -2.7 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -2.3 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -4.0 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -3.4 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -3.5 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -3.9 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -4.5 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -5.1 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -5.1 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -4.8 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -4.7 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -3.8 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -3.1 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -3.8 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in CAT Total Score | Day 28, n=234, 19, 86, 80, 77, 74, 229 | -4.7 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in CAT Total Score | Day 84, n=218, 17, 75, 75, 69, 62, 213 | -4.2 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in CAT Total Score | Day 56, n=231, 20, 78, 77, 76, 69, 222 | -4.4 Scores on a scale |
95% CI: [-0.5, 5.2]
95% CI: [-0.8, 2.3]
95% CI: [-0.8, 2.4]
95% CI: [-2, 1.2]
95% CI: [0, 3.3]
95% CI: [-1.1, 1.1]
95% CI: [-0.5, 5.4]
95% CI: [-0.9, 2.4]
95% CI: [-1.9, 1.4]
95% CI: [-2.3, 1]
95% CI: [-1.2, 2.2]
95% CI: [-1.4, 1]
95% CI: [-1.4, 5.1]
95% CI: [-0.7, 2.8]
95% CI: [-2.3, 1.1]
95% CI: [-1.9, 1.7]
95% CI: [-0.9, 2.8]
95% CI: [-0.8, 1.7]
Secondary
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1.
Time frame: Baseline and Days 14, 28, 56 (pre and post bronchodilaor), 84 (pre-bronchodilator) and at hospital discharge (maximum 24 Weeks)
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.036 Liters | Standard Deviation 0.2647 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.000 Liters | Standard Deviation 0.2566 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.017 Liters | Standard Deviation 0.2585 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | 0.005 Liters | Standard Deviation 0.2295 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.071 Liters | Standard Deviation 0.1586 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | 0.020 Liters | Standard Deviation 0.2614 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | 0.134 Liters | Standard Deviation 0.1514 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.034 Liters | Standard Deviation 0.2707 |
| Placebo | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.008 Liters | Standard Deviation 0.2729 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | -0.002 Liters | Standard Deviation 0.2252 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | -0.006 Liters | Standard Deviation 0.2636 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | 0.153 Liters | Standard Deviation 0.0933 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.075 Liters | Standard Deviation 0.2425 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.168 Liters | Standard Deviation 0.2652 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.081 Liters | Standard Deviation 0.2661 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.100 Liters | Standard Deviation 0.2511 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.003 Liters | Standard Deviation 0.2232 |
| Nemiralisib 12.5 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.059 Liters | Standard Deviation 0.2575 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | -0.049 Liters | Standard Deviation 0.2549 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | -0.024 Liters | Standard Deviation 0.321 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | -0.021 Liters | Standard Deviation 0.2657 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.010 Liters | Standard Deviation 0.2168 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | -0.012 Liters | Standard Deviation 0.2524 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.108 Liters | Standard Deviation 0.3888 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.004 Liters | Standard Deviation 0.2183 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | -0.034 Liters | Standard Deviation 0.2875 |
| Nemiralisib 50 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | 0.083 Liters | — |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | 0.004 Liters | Standard Deviation 0.2373 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | -0.013 Liters | Standard Deviation 0.2509 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | -0.050 Liters | Standard Deviation 0.2477 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | -0.010 Liters | Standard Deviation 0.2333 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | -0.034 Liters | Standard Deviation 0.2401 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | 0.011 Liters | Standard Deviation 0.2415 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.005 Liters | Standard Deviation 0.2668 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.056 Liters | Standard Deviation 0.1782 |
| Nemiralisib 100 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | -0.076 Liters | — |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | 0.094 Liters | — |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.049 Liters | Standard Deviation 0.2639 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.053 Liters | Standard Deviation 0.2958 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.064 Liters | Standard Deviation 0.2592 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | 0.022 Liters | Standard Deviation 0.2522 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | 0.026 Liters | Standard Deviation 0.2556 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.015 Liters | Standard Deviation 0.2739 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.054 Liters | Standard Deviation 0.2983 |
| Nemiralisib 250 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.052 Liters | Standard Deviation 0.3481 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.162 Liters | Standard Deviation 0.1426 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.027 Liters | Standard Deviation 0.2369 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.016 Liters | Standard Deviation 0.2713 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.041 Liters | Standard Deviation 0.2738 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.073 Liters | Standard Deviation 0.2655 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | -0.004 Liters | Standard Deviation 0.2233 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.007 Liters | Standard Deviation 0.2461 |
| Nemiralisib 500 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | -0.011 Liters | Standard Deviation 0.226 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.044 Liters | Standard Deviation 0.2216 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | 0.011 Liters | Standard Deviation 0.247 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.020 Liters | Standard Deviation 0.2512 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | -0.006 Liters | Standard Deviation 0.1079 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.010 Liters | Standard Deviation 0.2829 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.029 Liters | Standard Deviation 0.2307 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.075 Liters | Standard Deviation 0.1974 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.023 Liters | Standard Deviation 0.2561 |
| Nemiralisib 750 mcg | Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | -0.001 Liters | Standard Deviation 0.2858 |
Secondary
Change From Baseline in SGRQ Total Score at Days 28, 56 and 84
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100 multiplied by summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is defined as SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented
Time frame: Baseline and Days 28, 56 and 84
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -9.1 Scores on a scale |
| Placebo | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -7.7 Scores on a scale |
| Placebo | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -8.0 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -5.7 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -3.9 Scores on a scale |
| Nemiralisib 12.5 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -6.6 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -9.3 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -9.3 Scores on a scale |
| Nemiralisib 50 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -8.2 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -10.7 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -11.3 Scores on a scale |
| Nemiralisib 100 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -10.6 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -10.9 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -11.3 Scores on a scale |
| Nemiralisib 250 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -10.9 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -8.9 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -9.4 Scores on a scale |
| Nemiralisib 500 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -7.8 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 84, n=218, 17, 74, 74, 69, 60, 209 | -7.9 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 28, n=232, 19, 86, 78, 77, 72, 225 | -7.9 Scores on a scale |
| Nemiralisib 750 mcg | Change From Baseline in SGRQ Total Score at Days 28, 56 and 84 | Day 56, n=227, 20, 78, 77, 74, 68, 219 | -8.4 Scores on a scale |
95% CI: [-4.8, 8.3]
95% CI: [-4, 3.1]
95% CI: [-6.2, 1.1]
95% CI: [-6.7, 0.4]
95% CI: [-4, 3.5]
95% CI: [-2.7, 2.3]
95% CI: [-2.5, 11]
95% CI: [-4.8, 2.5]
95% CI: [-6.3, 1.1]
95% CI: [-7.3, 0.4]
95% CI: [-4.6, 3]
95% CI: [-2.9, 2.5]
95% CI: [-4.8, 9.4]
95% CI: [-4.1, 3.6]
95% CI: [-6.1, 1.8]
95% CI: [-5.7, 2.3]
95% CI: [-4.5, 3.8]
95% CI: [-1.7, 4]
Secondary
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10 to 30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1.
Time frame: Baseline and pre- and post-bronchodilator on Days 14, 28, 56 and 84
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | -0.039 Liters | Standard Deviation 0.261 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.034 Liters | Standard Deviation 0.2779 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.026 Liters | Standard Deviation 0.2691 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.082 Liters | Standard Deviation 0.2783 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | 0.007 Liters | Standard Deviation 0.2741 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | -0.014 Liters | Standard Deviation 0.2896 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | 0.019 Liters | Standard Deviation 0.2282 |
| Placebo | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | 0.056 Liters | Standard Deviation 0.3372 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | -0.027 Liters | Standard Deviation 0.4554 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.355 Liters | Standard Deviation 0.4207 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | 0.431 Liters | Standard Deviation 0.519 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.261 Liters | Standard Deviation 0.5204 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.334 Liters | Standard Deviation 0.5614 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | 0.106 Liters | Standard Deviation 0.6138 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | 0.139 Liters | Standard Deviation 0.6838 |
| Nemiralisib 12.5 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | 0.133 Liters | Standard Deviation 0.5162 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | 0.121 Liters | Standard Deviation 0.277 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | 0.042 Liters | Standard Deviation 0.3068 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | 0.019 Liters | Standard Deviation 0.3509 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.069 Liters | Standard Deviation 0.3012 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | 0.119 Liters | — |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.012 Liters | Standard Deviation 0.291 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.130 Liters | Standard Deviation 0.2327 |
| Nemiralisib 50 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | 0.037 Liters | Standard Deviation 0.3341 |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | -0.085 Liters | Standard Deviation 0.2072 |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | 0.108 Liters | — |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.130 Liters | — |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | 0.014 Liters | Standard Deviation 0.1938 |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | 0.098 Liters | — |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | -0.049 Liters | Standard Deviation 0.1882 |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | -0.081 Liters | Standard Deviation 0.1738 |
| Nemiralisib 100 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | 0.310 Liters | — |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | -0.074 Liters | Standard Deviation 0.3847 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | -0.056 Liters | Standard Deviation 0.3572 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | -0.069 Liters | Standard Deviation 0.4905 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.012 Liters | Standard Deviation 0.402 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.009 Liters | Standard Deviation 0.2006 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | -0.072 Liters | Standard Deviation 0.4391 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | 0.021 Liters | Standard Deviation 0.3151 |
| Nemiralisib 250 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | -0.305 Liters | — |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | -0.042 Liters | Standard Deviation 0.184 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.173 Liters | Standard Deviation 0.5137 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | 0.006 Liters | Standard Deviation 0.218 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.007 Liters | Standard Deviation 0.3237 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | 0.043 Liters | Standard Deviation 0.2511 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.030 Liters | Standard Deviation 0.4029 |
| Nemiralisib 500 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | -0.072 Liters | Standard Deviation 0.149 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | -0.046 Liters | Standard Deviation 0.2639 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | -0.062 Liters | Standard Deviation 0.2816 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | -0.106 Liters | Standard Deviation 0.2956 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.002 Liters | Standard Deviation 0.2343 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | -0.094 Liters | Standard Deviation 0.2293 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | -0.135 Liters | Standard Deviation 0.241 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | -0.054 Liters | Standard Deviation 0.2942 |
| Nemiralisib 750 mcg | Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator | Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | -0.021 Liters | Standard Deviation 0.1326 |
Secondary
Mean Number of Occasions of Rescue Medication Use Per Day
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.666 No. of occasions of rescue use per day | Standard Deviation 1.7913 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.729 No. of occasions of rescue use per day | Standard Deviation 1.8157 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.684 No. of occasions of rescue use per day | Standard Deviation 1.6903 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.698 No. of occasions of rescue use per day | Standard Deviation 1.9023 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.699 No. of occasions of rescue use per day | Standard Deviation 1.7674 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.684 No. of occasions of rescue use per day | Standard Deviation 1.7706 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.729 No. of occasions of rescue use per day | Standard Deviation 1.9406 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.650 No. of occasions of rescue use per day | Standard Deviation 1.8711 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.703 No. of occasions of rescue use per day | Standard Deviation 1.9914 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.741 No. of occasions of rescue use per day | Standard Deviation 1.9543 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.708 No. of occasions of rescue use per day | Standard Deviation 1.8709 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.735 No. of occasions of rescue use per day | Standard Deviation 1.8662 |
| Placebo | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.656 No. of occasions of rescue use per day | Standard Deviation 1.8606 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 2.164 No. of occasions of rescue use per day | Standard Deviation 2.2504 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 2.736 No. of occasions of rescue use per day | Standard Deviation 3.1579 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 2.479 No. of occasions of rescue use per day | Standard Deviation 2.6976 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 2.231 No. of occasions of rescue use per day | Standard Deviation 2.7169 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 2.386 No. of occasions of rescue use per day | Standard Deviation 2.8157 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 2.021 No. of occasions of rescue use per day | Standard Deviation 2.2926 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 2.112 No. of occasions of rescue use per day | Standard Deviation 2.2977 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 2.190 No. of occasions of rescue use per day | Standard Deviation 2.3657 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 2.543 No. of occasions of rescue use per day | Standard Deviation 2.8753 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 2.329 No. of occasions of rescue use per day | Standard Deviation 2.6394 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 2.330 No. of occasions of rescue use per day | Standard Deviation 2.4715 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 2.765 No. of occasions of rescue use per day | Standard Deviation 3.1104 |
| Nemiralisib 12.5 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 2.378 No. of occasions of rescue use per day | Standard Deviation 2.6904 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.633 No. of occasions of rescue use per day | Standard Deviation 1.432 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.495 No. of occasions of rescue use per day | Standard Deviation 1.3943 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.414 No. of occasions of rescue use per day | Standard Deviation 1.392 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.469 No. of occasions of rescue use per day | Standard Deviation 1.4036 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.533 No. of occasions of rescue use per day | Standard Deviation 1.5706 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.531 No. of occasions of rescue use per day | Standard Deviation 1.6374 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.608 No. of occasions of rescue use per day | Standard Deviation 1.7699 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.553 No. of occasions of rescue use per day | Standard Deviation 1.5884 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.404 No. of occasions of rescue use per day | Standard Deviation 1.4897 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.382 No. of occasions of rescue use per day | Standard Deviation 1.4 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.514 No. of occasions of rescue use per day | Standard Deviation 1.5022 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.553 No. of occasions of rescue use per day | Standard Deviation 1.4044 |
| Nemiralisib 50 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.589 No. of occasions of rescue use per day | Standard Deviation 1.6571 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.697 No. of occasions of rescue use per day | Standard Deviation 2.0769 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.926 No. of occasions of rescue use per day | Standard Deviation 2.1569 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.712 No. of occasions of rescue use per day | Standard Deviation 2.031 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.693 No. of occasions of rescue use per day | Standard Deviation 1.9679 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.720 No. of occasions of rescue use per day | Standard Deviation 2.0083 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.750 No. of occasions of rescue use per day | Standard Deviation 2.038 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.792 No. of occasions of rescue use per day | Standard Deviation 2.0822 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.616 No. of occasions of rescue use per day | Standard Deviation 1.9444 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.658 No. of occasions of rescue use per day | Standard Deviation 2.0646 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.596 No. of occasions of rescue use per day | Standard Deviation 1.9809 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.602 No. of occasions of rescue use per day | Standard Deviation 1.9435 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.671 No. of occasions of rescue use per day | Standard Deviation 1.9612 |
| Nemiralisib 100 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.750 No. of occasions of rescue use per day | Standard Deviation 1.9048 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.489 No. of occasions of rescue use per day | Standard Deviation 1.6734 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.672 No. of occasions of rescue use per day | Standard Deviation 1.9447 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.546 No. of occasions of rescue use per day | Standard Deviation 1.8824 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.572 No. of occasions of rescue use per day | Standard Deviation 1.8294 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.620 No. of occasions of rescue use per day | Standard Deviation 1.5994 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.488 No. of occasions of rescue use per day | Standard Deviation 1.6611 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.535 No. of occasions of rescue use per day | Standard Deviation 1.8384 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.670 No. of occasions of rescue use per day | Standard Deviation 1.5728 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.720 No. of occasions of rescue use per day | Standard Deviation 1.8918 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.636 No. of occasions of rescue use per day | Standard Deviation 1.8042 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.712 No. of occasions of rescue use per day | Standard Deviation 1.9532 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.497 No. of occasions of rescue use per day | Standard Deviation 1.57 |
| Nemiralisib 250 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.628 No. of occasions of rescue use per day | Standard Deviation 1.8741 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.742 No. of occasions of rescue use per day | Standard Deviation 1.838 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 2.006 No. of occasions of rescue use per day | Standard Deviation 2.2242 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.949 No. of occasions of rescue use per day | Standard Deviation 1.9685 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.953 No. of occasions of rescue use per day | Standard Deviation 2.1838 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 2.009 No. of occasions of rescue use per day | Standard Deviation 2.0506 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.927 No. of occasions of rescue use per day | Standard Deviation 2.1613 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.917 No. of occasions of rescue use per day | Standard Deviation 1.9298 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.926 No. of occasions of rescue use per day | Standard Deviation 2.3243 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.611 No. of occasions of rescue use per day | Standard Deviation 1.7717 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.921 No. of occasions of rescue use per day | Standard Deviation 1.9201 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.790 No. of occasions of rescue use per day | Standard Deviation 2.114 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.899 No. of occasions of rescue use per day | Standard Deviation 2.1694 |
| Nemiralisib 500 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.936 No. of occasions of rescue use per day | Standard Deviation 2.0729 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.824 No. of occasions of rescue use per day | Standard Deviation 1.8397 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.707 No. of occasions of rescue use per day | Standard Deviation 1.7512 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.826 No. of occasions of rescue use per day | Standard Deviation 1.8778 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.775 No. of occasions of rescue use per day | Standard Deviation 1.8753 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.780 No. of occasions of rescue use per day | Standard Deviation 1.8083 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.731 No. of occasions of rescue use per day | Standard Deviation 1.7245 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.747 No. of occasions of rescue use per day | Standard Deviation 1.7332 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.655 No. of occasions of rescue use per day | Standard Deviation 1.743 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.705 No. of occasions of rescue use per day | Standard Deviation 1.7646 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.733 No. of occasions of rescue use per day | Standard Deviation 1.6618 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.737 No. of occasions of rescue use per day | Standard Deviation 1.803 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.716 No. of occasions of rescue use per day | Standard Deviation 1.7421 |
| Nemiralisib 750 mcg | Mean Number of Occasions of Rescue Medication Use Per Day | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.587 No. of occasions of rescue use per day | Standard Deviation 1.6531 |
Secondary
Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT
Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation.
Time frame: Up to Week 12
Population: Severity was derived for participants from MITT Population who had reported subsequent exacerbation. Only those participants with data available at specified data points were analyzed (represented by n=X in the category title).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 54.0 Scores on a scale | Standard Deviation 15.53 |
| Placebo | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 53.1 Scores on a scale | Standard Deviation 11.54 |
| Placebo | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 53.3 Scores on a scale | Standard Deviation 12.16 |
| Nemiralisib 12.5 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 60.0 Scores on a scale | Standard Deviation 26.56 |
| Nemiralisib 12.5 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 64.6 Scores on a scale | Standard Deviation 25.2 |
| Nemiralisib 12.5 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 83.0 Scores on a scale | — |
| Nemiralisib 50 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 64.0 Scores on a scale | Standard Deviation 15.01 |
| Nemiralisib 50 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 59.8 Scores on a scale | Standard Deviation 12.82 |
| Nemiralisib 50 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 57.4 Scores on a scale | Standard Deviation 11.08 |
| Nemiralisib 100 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 50.0 Scores on a scale | Standard Deviation 11.15 |
| Nemiralisib 100 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 50.5 Scores on a scale | Standard Deviation 10.76 |
| Nemiralisib 100 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 55.3 Scores on a scale | Standard Deviation 5.69 |
| Nemiralisib 250 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 46.3 Scores on a scale | Standard Deviation 14.2 |
| Nemiralisib 250 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 47.5 Scores on a scale | Standard Deviation 13.95 |
| Nemiralisib 250 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 49.5 Scores on a scale | Standard Deviation 13.95 |
| Nemiralisib 500 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 57.6 Scores on a scale | Standard Deviation 10.3 |
| Nemiralisib 500 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 64.1 Scores on a scale | Standard Deviation 8.99 |
| Nemiralisib 500 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 53.8 Scores on a scale | Standard Deviation 9.28 |
| Nemiralisib 750 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Severe, n=13, 1, 9, 3, 10, 6, 20 | 58.8 Scores on a scale | Standard Deviation 10.34 |
| Nemiralisib 750 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate, n=55, 3, 15, 23, 17, 10, 63 | 50.0 Scores on a scale | Standard Deviation 10.17 |
| Nemiralisib 750 mcg | Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT | Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 51.9 Scores on a scale | Standard Deviation 10.78 |
Secondary
Number of Participants Reporting COPD Exacerbations
Participants reporting acute COPD exacerbations during the study period has been presented.
Time frame: Up to Week 16
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Reporting COPD Exacerbations | 8 Participants |
| Nemiralisib 12.5 mcg | Number of Participants Reporting COPD Exacerbations | 1 Participants |
| Nemiralisib 50 mcg | Number of Participants Reporting COPD Exacerbations | 6 Participants |
| Nemiralisib 100 mcg | Number of Participants Reporting COPD Exacerbations | 4 Participants |
| Nemiralisib 250 mcg | Number of Participants Reporting COPD Exacerbations | 4 Participants |
| Nemiralisib 500 mcg | Number of Participants Reporting COPD Exacerbations | 3 Participants |
| Nemiralisib 750 mcg | Number of Participants Reporting COPD Exacerbations | 17 Participants |
Secondary
Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI)
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received.
Time frame: Up to Week 24
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 9 Participants |
| Placebo | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 23 Participants |
| Placebo | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 31 Participants |
| Nemiralisib 12.5 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 2 Participants |
| Nemiralisib 12.5 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 1 Participants |
| Nemiralisib 12.5 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 10 Participants |
| Nemiralisib 50 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 14 Participants |
| Nemiralisib 50 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 9 Participants |
| Nemiralisib 100 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 13 Participants |
| Nemiralisib 100 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 19 Participants |
| Nemiralisib 100 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 10 Participants |
| Nemiralisib 250 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 16 Participants |
| Nemiralisib 250 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 25 Participants |
| Nemiralisib 250 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 21 Participants |
| Nemiralisib 500 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 36 Participants |
| Nemiralisib 500 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 29 Participants |
| Nemiralisib 500 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 6 Participants |
| Nemiralisib 750 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any AESI | 93 Participants |
| Nemiralisib 750 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any SAE | 26 Participants |
| Nemiralisib 750 mcg | Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI) | Any non-SAE | 101 Participants |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented.
Time frame: Screening, Days 14, 84, 112 and at early withdrawal
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 79 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 93 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 3 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 88 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 77 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 8 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 8 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 11 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 10 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 2 Participants |
| Nemiralisib 50 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 24 Participants |
| Nemiralisib 50 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 25 Participants |
| Nemiralisib 50 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 22 Participants |
| Nemiralisib 50 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 28 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 27 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 37 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 33 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 28 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 1 Participants |
| Nemiralisib 250 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 28 Participants |
| Nemiralisib 250 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 3 Participants |
| Nemiralisib 250 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 24 Participants |
| Nemiralisib 250 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 25 Participants |
| Nemiralisib 250 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 29 Participants |
| Nemiralisib 500 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 21 Participants |
| Nemiralisib 500 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 1 Participants |
| Nemiralisib 500 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 20 Participants |
| Nemiralisib 500 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 18 Participants |
| Nemiralisib 500 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 18 Participants |
| Nemiralisib 750 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 112 | 75 Participants |
| Nemiralisib 750 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 14 | 74 Participants |
| Nemiralisib 750 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 84 | 64 Participants |
| Nemiralisib 750 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Screening | 86 Participants |
| Nemiralisib 750 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Early withdrawal | 4 Participants |
Secondary
Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation
Number of participants with time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Up to Week 12
Population: MITT Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 72 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 3 Participants |
| Nemiralisib 50 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 24 Participants |
| Nemiralisib 100 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 25 Participants |
| Nemiralisib 250 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 26 Participants |
| Nemiralisib 500 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 15 Participants |
| Nemiralisib 750 mcg | Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 80 Participants |
95% CI: [0.054, 1.103]
95% CI: [0.58, 1.5]
95% CI: [0.581, 1.467]
95% CI: [0.682, 1.709]
95% CI: [0.268, 0.902]
95% CI: [0.8, 1.539]
Secondary
Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool
Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score \>=9 points from the Maximum Observed Value, sustained for \>=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented.
Time frame: From randomization to Week 12
Population: MITT Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 141 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 11 Participants |
| Nemiralisib 50 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 54 Participants |
| Nemiralisib 100 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 50 Participants |
| Nemiralisib 250 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 45 Participants |
| Nemiralisib 500 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 34 Participants |
| Nemiralisib 750 mcg | Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 149 Participants |
95% CI: [0.477, 1.765]
95% CI: [0.84, 1.597]
95% CI: [0.734, 1.432]
95% CI: [0.719, 1.413]
95% CI: [0.487, 1.057]
95% CI: [0.899, 1.426]
Secondary
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values
Blood samples were collected for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Upto Week 16
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 27 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 2 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 2 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 264 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 237 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 7 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 264 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 2 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 1 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 266 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 265 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 266 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 3 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 256 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 3 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 18 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 21 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 81 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 91 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 1 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 90 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 10 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 88 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 90 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 91 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 3 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 90 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 90 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 90 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 82 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 86 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 90 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 90 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 89 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 7 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 1 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 87 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 1 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 87 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 87 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 2 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 85 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 1 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 80 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 85 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 4 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 86 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 3 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 1 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 84 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 1 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 84 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 9 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 76 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 85 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 84 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 1 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 85 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 3 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 82 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To high, n=266,21,90,90,87,85,263 | 1 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 262 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 263 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 2 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 6 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To high, n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 231 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 32 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To high, n=266,21,90,90,87,85,263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,To high, n=266,21,91,90,87,85,263 | 4 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 253 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 262 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 1 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,To high,n=266,21,91,90,87,85,263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 263 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 261 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Clinical Chemistry Values | Sod,To high, n=266,21,91,90,87,85,263 | 0 Participants |
Secondary
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate
The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Up to Week 16
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 265 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 3 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 250 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 260 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 1 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 5 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 11 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 8 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 10 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 1 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 17 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 18 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 3 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 1 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 2 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 21 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 83 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 7 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 84 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 3 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 5 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 85 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 3 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 3 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 82 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 3 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 7 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 91 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 90 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 79 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 8 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 5 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 82 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 4 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 6 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 2 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 79 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 83 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 6 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 3 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 2 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 82 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 80 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 4 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 5 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To high | 19 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To low | 7 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To within range/no change | 256 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | DBP, To high | 3 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To low | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate,To within range/no change | 258 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | Pulse rate, To high | 8 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To low | 8 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate | SBP, To withinn range/no change | 239 Participants |
Secondary
Number of Participants With Worst Case Post Baseline Hematology Values
Blood samples were collected for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the To w/in Range or No Change category. Participants are counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Upto Week 16
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 38 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 239 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 9 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 260 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 253 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 211 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 3 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 215 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 48 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 8 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 17 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 19 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 19 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 3 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 1 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 16 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 4 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 20 Participants |
| Nemiralisib 12.5 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 6 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 73 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 1 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 81 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 90 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 79 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 9 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 0 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 88 Participants |
| Nemiralisib 50 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 11 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 90 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 76 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 11 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 76 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 16 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 5 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 74 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 7 Participants |
| Nemiralisib 100 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 90 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 68 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 7 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 70 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 20 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 63 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 5 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 84 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 14 Participants |
| Nemiralisib 250 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 84 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 62 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 16 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 60 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 81 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 73 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 2 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 78 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 17 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 0 Participants |
| Nemiralisib 500 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 2 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To high,n=256,20,85,88,82,77,249 | 12 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 11 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 201 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To high, n=259,20,90,90,83,78,251 | 50 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 253 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,To high, n=256,20,85,88,82,77,249 | 34 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 1 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 226 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,To high, n=253,19,88,90,84,78,245 | 0 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 245 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu, To low, n=256,20,85,88,82,77,249 | 2 Participants |
| Nemiralisib 750 mcg | Number of Participants With Worst Case Post Baseline Hematology Values | Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 213 Participants |
Secondary
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation
EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score \>=9 points from maximum observed value, sustained for \>=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender.
Time frame: Days 14, 28, 56 and 84
Population: MITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 29 Percentage of participants |
| Placebo | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 40 Percentage of participants |
| Placebo | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 49 Percentage of participants |
| Placebo | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 51 Percentage of participants |
| Nemiralisib 12.5 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 50 Percentage of participants |
| Nemiralisib 12.5 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 45 Percentage of participants |
| Nemiralisib 12.5 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 27 Percentage of participants |
| Nemiralisib 12.5 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 41 Percentage of participants |
| Nemiralisib 50 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 59 Percentage of participants |
| Nemiralisib 50 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 52 Percentage of participants |
| Nemiralisib 50 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 37 Percentage of participants |
| Nemiralisib 50 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 59 Percentage of participants |
| Nemiralisib 100 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 29 Percentage of participants |
| Nemiralisib 100 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 43 Percentage of participants |
| Nemiralisib 100 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 52 Percentage of participants |
| Nemiralisib 100 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 54 Percentage of participants |
| Nemiralisib 250 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 28 Percentage of participants |
| Nemiralisib 250 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 50 Percentage of participants |
| Nemiralisib 250 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 42 Percentage of participants |
| Nemiralisib 250 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 50 Percentage of participants |
| Nemiralisib 500 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 27 Percentage of participants |
| Nemiralisib 500 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 24 Percentage of participants |
| Nemiralisib 500 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 31 Percentage of participants |
| Nemiralisib 500 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 37 Percentage of participants |
| Nemiralisib 750 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 56 | 50 Percentage of participants |
| Nemiralisib 750 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 14 | 32 Percentage of participants |
| Nemiralisib 750 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 28 | 42 Percentage of participants |
| Nemiralisib 750 mcg | Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation | Day 84 | 54 Percentage of participants |
95% CI: [0.21, 2.3]
95% CI: [0.76, 2.17]
95% CI: [0.54, 1.61]
95% CI: [0.5, 1.49]
95% CI: [0.38, 1.25]
95% CI: [0.77, 1.63]
95% CI: [0.36, 2.69]
95% CI: [0.82, 2.33]
95% CI: [0.67, 1.79]
95% CI: [0.63, 1.74]
95% CI: [0.28, 0.88]
95% CI: [0.72, 1.49]
95% CI: [0.3, 2.17]
95% CI: [0.84, 2.27]
95% CI: [0.65, 1.78]
95% CI: [0.62, 1.67]
95% CI: [0.26, 0.77]
95% CI: [0.71, 1.42]
95% CI: [0.32, 2.38]
95% CI: [0.7, 2]
95% CI: [0.63, 1.71]
95% CI: [0.55, 1.48]
95% CI: [0.31, 0.87]
95% CI: [0.73, 1.47]
Secondary
Percentage of Rescue-free Days
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period
Population: MITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 41.390 Percentage of rescue free days | Standard Deviation 40.8871 |
| Placebo | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 38.204 Percentage of rescue free days | Standard Deviation 39.0621 |
| Placebo | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 39.743 Percentage of rescue free days | Standard Deviation 36.8957 |
| Placebo | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 40.608 Percentage of rescue free days | Standard Deviation 41.0492 |
| Placebo | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 34.898 Percentage of rescue free days | Standard Deviation 37.7118 |
| Placebo | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 39.678 Percentage of rescue free days | Standard Deviation 40.8359 |
| Placebo | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 39.701 Percentage of rescue free days | Standard Deviation 41.9689 |
| Placebo | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 41.002 Percentage of rescue free days | Standard Deviation 40.9566 |
| Placebo | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 41.373 Percentage of rescue free days | Standard Deviation 43.4266 |
| Placebo | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 40.287 Percentage of rescue free days | Standard Deviation 42.2167 |
| Placebo | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 39.268 Percentage of rescue free days | Standard Deviation 40.53 |
| Placebo | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 38.262 Percentage of rescue free days | Standard Deviation 40.7807 |
| Placebo | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 42.058 Percentage of rescue free days | Standard Deviation 41.2168 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 38.575 Percentage of rescue free days | Standard Deviation 44.2366 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 34.290 Percentage of rescue free days | Standard Deviation 42.83 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 32.145 Percentage of rescue free days | Standard Deviation 43.1992 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 40.819 Percentage of rescue free days | Standard Deviation 46.7899 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 39.415 Percentage of rescue free days | Standard Deviation 45.0442 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 38.776 Percentage of rescue free days | Standard Deviation 44.0612 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 36.076 Percentage of rescue free days | Standard Deviation 44.3182 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 35.376 Percentage of rescue free days | Standard Deviation 43.9405 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 35.000 Percentage of rescue free days | Standard Deviation 42.343 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 35.005 Percentage of rescue free days | Standard Deviation 41.8344 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 35.533 Percentage of rescue free days | Standard Deviation 39.0694 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 32.145 Percentage of rescue free days | Standard Deviation 44.6657 |
| Nemiralisib 12.5 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 37.870 Percentage of rescue free days | Standard Deviation 40.2125 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 29.849 Percentage of rescue free days | Standard Deviation 38.3385 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 31.643 Percentage of rescue free days | Standard Deviation 38.0943 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 37.369 Percentage of rescue free days | Standard Deviation 40.2613 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 32.145 Percentage of rescue free days | Standard Deviation 41.2227 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 35.552 Percentage of rescue free days | Standard Deviation 40.5745 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 35.634 Percentage of rescue free days | Standard Deviation 41.3319 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 32.759 Percentage of rescue free days | Standard Deviation 39.2972 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 33.029 Percentage of rescue free days | Standard Deviation 41.0867 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 35.624 Percentage of rescue free days | Standard Deviation 42.6625 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 35.384 Percentage of rescue free days | Standard Deviation 40.9175 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 32.531 Percentage of rescue free days | Standard Deviation 39.0078 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 33.590 Percentage of rescue free days | Standard Deviation 36.6456 |
| Nemiralisib 50 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 32.456 Percentage of rescue free days | Standard Deviation 40.7192 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 45.266 Percentage of rescue free days | Standard Deviation 43.591 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 33.392 Percentage of rescue free days | Standard Deviation 39.7372 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 43.017 Percentage of rescue free days | Standard Deviation 43.9884 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 39.964 Percentage of rescue free days | Standard Deviation 40.3936 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 42.202 Percentage of rescue free days | Standard Deviation 43.0692 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 41.682 Percentage of rescue free days | Standard Deviation 41.3648 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 41.720 Percentage of rescue free days | Standard Deviation 44.0117 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 44.118 Percentage of rescue free days | Standard Deviation 41.6682 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 42.505 Percentage of rescue free days | Standard Deviation 41.2121 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 43.396 Percentage of rescue free days | Standard Deviation 42.304 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 42.859 Percentage of rescue free days | Standard Deviation 41.7845 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 41.300 Percentage of rescue free days | Standard Deviation 39.8199 |
| Nemiralisib 100 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 40.441 Percentage of rescue free days | Standard Deviation 37.6285 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 43.194 Percentage of rescue free days | Standard Deviation 41.0201 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 39.337 Percentage of rescue free days | Standard Deviation 42.3061 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 41.492 Percentage of rescue free days | Standard Deviation 42.1984 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 42.918 Percentage of rescue free days | Standard Deviation 42.8354 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 39.631 Percentage of rescue free days | Standard Deviation 36.5157 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 41.191 Percentage of rescue free days | Standard Deviation 42.1751 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 41.026 Percentage of rescue free days | Standard Deviation 42.1584 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 32.583 Percentage of rescue free days | Standard Deviation 38.3577 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 39.476 Percentage of rescue free days | Standard Deviation 42.2376 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 39.196 Percentage of rescue free days | Standard Deviation 41.6575 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 39.981 Percentage of rescue free days | Standard Deviation 40.8296 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 38.573 Percentage of rescue free days | Standard Deviation 40.3629 |
| Nemiralisib 250 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 40.409 Percentage of rescue free days | Standard Deviation 42.056 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 34.923 Percentage of rescue free days | Standard Deviation 40.4026 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 34.811 Percentage of rescue free days | Standard Deviation 39.3585 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 33.912 Percentage of rescue free days | Standard Deviation 37.9973 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 36.823 Percentage of rescue free days | Standard Deviation 42.3513 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 30.986 Percentage of rescue free days | Standard Deviation 38.5941 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 37.024 Percentage of rescue free days | Standard Deviation 41.2291 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 34.453 Percentage of rescue free days | Standard Deviation 35.9802 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 39.841 Percentage of rescue free days | Standard Deviation 43.7237 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 40.595 Percentage of rescue free days | Standard Deviation 41.1717 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 35.820 Percentage of rescue free days | Standard Deviation 34.6377 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 42.236 Percentage of rescue free days | Standard Deviation 42.1567 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 38.232 Percentage of rescue free days | Standard Deviation 41.0296 |
| Nemiralisib 500 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 35.519 Percentage of rescue free days | Standard Deviation 42.2122 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 8, n=250, 20, 84, 83, 77, 71, 231 | 32.357 Percentage of rescue free days | Standard Deviation 39.9221 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 4, n=250, 21, 89, 87, 81, 77, 243 | 32.394 Percentage of rescue free days | Standard Deviation 39.0174 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 7, n=250, 20, 85, 83, 77, 71, 231 | 31.975 Percentage of rescue free days | Standard Deviation 39.491 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 9, n=244, 20, 82, 81, 76, 71, 229 | 33.606 Percentage of rescue free days | Standard Deviation 39.469 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 6, n=250, 20, 86, 84, 78, 72, 234 | 32.351 Percentage of rescue free days | Standard Deviation 39.2542 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 12, n=240, 20, 78, 80, 73, 70, 225 | 33.906 Percentage of rescue free days | Standard Deviation 38.4851 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 1, n=254, 21, 87, 88, 80, 79, 254 | 29.779 Percentage of rescue free days | Standard Deviation 36.1498 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 3, n=256, 21, 90, 88, 80, 81, 245 | 33.006 Percentage of rescue free days | Standard Deviation 38.4986 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 10, n=241, 20, 81, 80, 73, 71, 227 | 33.483 Percentage of rescue free days | Standard Deviation 40.1924 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 32.743 Percentage of rescue free days | Standard Deviation 33.9362 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 5, n=251, 20, 88, 85, 78, 76, 240 | 33.168 Percentage of rescue free days | Standard Deviation 39.0654 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 11, n=241, 20, 79, 80, 73, 71, 226 | 33.127 Percentage of rescue free days | Standard Deviation 39.1842 |
| Nemiralisib 750 mcg | Percentage of Rescue-free Days | Week 2, n=259, 21, 88, 89, 80, 82, 252 | 33.639 Percentage of rescue free days | Standard Deviation 38.9767 |
Secondary
Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score \>=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score \>=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Days 28, 56 and 84
Population: MITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 61 Percentage of responders |
| Placebo | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 50 Percentage of responders |
| Placebo | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 21 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 36 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 14 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 50 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 66 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 19 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 56 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 55 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 26 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 63 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 60 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 32 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 68 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 24 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 57 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 49 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 84 | 62 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 56 | 53 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84 | Day 28 | 21 Percentage of responders |
95% CI: [0.03, 1.41]
95% CI: [0.42, 1.47]
95% CI: [0.69, 2.24]
95% CI: [0.95, 2.91]
95% CI: [0.61, 2.08]
95% CI: [0.6, 1.4]
95% CI: [0.14, 1.16]
95% CI: [0.74, 1.98]
95% CI: [0.73, 1.97]
95% CI: [0.83, 2.27]
95% CI: [0.57, 1.62]
95% CI: [0.75, 1.5]
95% CI: [0.17, 1.39]
95% CI: [0.72, 2.01]
95% CI: [0.64, 1.79]
95% CI: [0.75, 2.14]
95% CI: [0.53, 1.45]
95% CI: [0.71, 1.43]
Secondary
Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score \>=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score \>=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Days 28, 56 and 84
Population: MITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 70 Percentage of responders |
| Placebo | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 63 Percentage of responders |
| Placebo | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 32 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 50 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 36 Percentage of responders |
| Nemiralisib 12.5 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 55 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 78 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 34 Percentage of responders |
| Nemiralisib 50 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 73 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 61 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 39 Percentage of responders |
| Nemiralisib 100 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 65 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 69 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 38 Percentage of responders |
| Nemiralisib 250 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 72 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 34 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 60 Percentage of responders |
| Nemiralisib 500 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 55 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 84 | 66 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 56 | 61 Percentage of responders |
| Nemiralisib 750 mcg | Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation | Day 28 | 25 Percentage of responders |
95% CI: [0.35, 2.7]
95% CI: [0.63, 1.77]
95% CI: [0.77, 2.17]
95% CI: [0.71, 2]
95% CI: [0.61, 1.75]
95% CI: [0.46, 0.99]
95% CI: [0.2, 1.41]
95% CI: [0.84, 2.46]
95% CI: [0.53, 1.48]
95% CI: [0.74, 2.16]
95% CI: [0.43, 1.17]
95% CI: [0.63, 1.27]
95% CI: [0.16, 1.2]
95% CI: [0.79, 2.56]
95% CI: [0.46, 1.3]
95% CI: [0.62, 1.86]
95% CI: [0.36, 1.02]
95% CI: [0.57, 1.17]
Secondary
Plasma Concentration of Nemiralisib
Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 113.6 Picograms per milliliter | Geometric Coefficient of Variation 6 |
| Placebo | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 54.9 Picograms per milliliter | Geometric Coefficient of Variation 43 |
| Placebo | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 35.0 Picograms per milliliter | Geometric Coefficient of Variation 57 |
| Placebo | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 23.6 Picograms per milliliter | Geometric Coefficient of Variation 24 |
| Placebo | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 36.2 Picograms per milliliter | Geometric Coefficient of Variation 26 |
| Placebo | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 28.1 Picograms per milliliter | Geometric Coefficient of Variation 15 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 109.9 Picograms per milliliter | Geometric Coefficient of Variation 51 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 60.5 Picograms per milliliter | Geometric Coefficient of Variation 45 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 85.4 Picograms per milliliter | Geometric Coefficient of Variation 40 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 62.0 Picograms per milliliter | Geometric Coefficient of Variation 46 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 93.1 Picograms per milliliter | Geometric Coefficient of Variation 58 |
| Nemiralisib 12.5 mcg | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 104.9 Picograms per milliliter | Geometric Coefficient of Variation 70 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 211.4 Picograms per milliliter | Geometric Coefficient of Variation 41 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 253.3 Picograms per milliliter | Geometric Coefficient of Variation 52 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 129.4 Picograms per milliliter | Geometric Coefficient of Variation 46 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 231.8 Picograms per milliliter | Geometric Coefficient of Variation 53 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 142.8 Picograms per milliliter | Geometric Coefficient of Variation 44 |
| Nemiralisib 50 mcg | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 253.7 Picograms per milliliter | Geometric Coefficient of Variation 73 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 315.6 Picograms per milliliter | Geometric Coefficient of Variation 85 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 767.6 Picograms per milliliter | Geometric Coefficient of Variation 71 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 657.0 Picograms per milliliter | Geometric Coefficient of Variation 61 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 598.8 Picograms per milliliter | Geometric Coefficient of Variation 39 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 807.0 Picograms per milliliter | Geometric Coefficient of Variation 66 |
| Nemiralisib 100 mcg | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 416.0 Picograms per milliliter | Geometric Coefficient of Variation 59 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 687.3 Picograms per milliliter | Geometric Coefficient of Variation 53 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 1552.2 Picograms per milliliter | Geometric Coefficient of Variation 83 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 1492.0 Picograms per milliliter | Geometric Coefficient of Variation 59 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 1146.7 Picograms per milliliter | Geometric Coefficient of Variation 56 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 528.3 Picograms per milliliter | Geometric Coefficient of Variation 110 |
| Nemiralisib 250 mcg | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 1079.5 Picograms per milliliter | Geometric Coefficient of Variation 80 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 937.6 Picograms per milliliter | Geometric Coefficient of Variation 101 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 1622.7 Picograms per milliliter | Geometric Coefficient of Variation 90 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 1717.6 Picograms per milliliter | Geometric Coefficient of Variation 114 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 1388.1 Picograms per milliliter | Geometric Coefficient of Variation 101 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 1972.0 Picograms per milliliter | Geometric Coefficient of Variation 110 |
| Nemiralisib 500 mcg | Plasma Concentration of Nemiralisib | Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 1069.6 Picograms per milliliter | Geometric Coefficient of Variation 70 |
Secondary
Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period
Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented.
Time frame: Up to Week 12
Population: MITT Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.31 No.of exacerbation per 84 Days |
| Nemiralisib 12.5 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | NA No.of exacerbation per 84 Days |
| Nemiralisib 50 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.29 No.of exacerbation per 84 Days |
| Nemiralisib 100 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.28 No.of exacerbation per 84 Days |
| Nemiralisib 250 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.32 No.of exacerbation per 84 Days |
| Nemiralisib 500 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.20 No.of exacerbation per 84 Days |
| Nemiralisib 750 mcg | Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.36 No.of exacerbation per 84 Days |
95% CI: [0.6, 1.4]
95% CI: [0.57, 1.35]
95% CI: [0.65, 1.5]
95% CI: [0.37, 1.02]
95% CI: [0.85, 1.52]
Other Pre-specified
Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 12.5 mcg | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 50 mcg | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 100 mcg | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 250 mcg | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 500 mcg | Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA Hours*picograms per milliliter |
Other Pre-specified
AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 12.5 mcg | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 50 mcg | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 100 mcg | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 250 mcg | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
| Nemiralisib 500 mcg | AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA Hours*picograms per milliliter |
Other Pre-specified
Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 12.5 mcg | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 50 mcg | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 100 mcg | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 250 mcg | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 500 mcg | Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA Picograms per milliliter |
Other Pre-specified
Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 12.5 mcg | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 50 mcg | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 100 mcg | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 250 mcg | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
| Nemiralisib 500 mcg | Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA Picograms per milliliter |
Other Pre-specified
Time to Reach Cmax (Tmax) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |
| Nemiralisib 12.5 mcg | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |
| Nemiralisib 50 mcg | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |
| Nemiralisib 100 mcg | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |
| Nemiralisib 250 mcg | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |
| Nemiralisib 500 mcg | Time to Reach Cmax (Tmax) of Nemiralisib | NA Hours |